Phosphorus oxychloride → HCID 66749241, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-(morpholin-4-yl)-4-(2-naphthylmethyl)-1,3-thiazole-5-carboxamide (229 mg, 0.648 mmol) (for amide coupling, see example 61-step 1) and phosphoryl chloride (4.00 mL, 42.9 mmol) was stirred at 80° C. for 30 min. The reaction slowly turned homogeneous. The resulting solution was concentrated under reduced pressure and carefully quenched with 1N NaOH solution at 0° C. The resulting mixture was distributed between 1N NaOH solution and EtOAc. The aqueous layer was extracted with EtOAc. The combined organic layer was dried and concentrated to provide 2-(morpholin-4-yl)-4-(2-naphthylmethyl)-1,3-thiazole-5-carbonitrile as a yellow solid (213 mg, 98.0% yield). LCMS: (AA) ES+ 336; 1H NMR (400 MHz, DMSO) δ 7.90-7.83 (dd, J=9.0, 1.9 Hz, 3H), 7.80-7.72 (s, 1H), 7.53-7.46 (m, 2H), 7.46-7.38 (m, 1H), 4.18-4.09 (s, 2H), 3.70-3.60 (t, J=4.9 Hz, 4H), 3.51-3.41 (t, J=4.9 Hz, 4H).

Provenance & Evidence